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Gene Review

GATA3  -  GATA binding protein 3

Homo sapiens

Synonyms: GATA-binding factor 3, HDR, HDRS, Trans-acting T-cell-specific transcription factor GATA-3
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Disease relevance of GATA3

  • Our data suggest that immunohistochemical analysis of GATA3 may be the basis for a new clinically applicable test to predict tumor recurrence early in the progression of breast cancer [1].
  • To validate its prognostic utility, we did a tissue microarray analysis on a cohort of 139 consecutive invasive carcinomas (n = 417 tissue samples) immunostained with a monoclonal antibody against GATA3 [1].
  • The hazard ratio of metastasis or recurrence according to the GATA3 status was 0.31 (95% confidence interval, 0.13-0.74; P = 0.009) [1].
  • Regulation of the human interleukin-5 promoter by Ets transcription factors. Ets1 and Ets2, but not Elf-1, cooperate with GATA3 and HTLV-I Tax1 [2].
  • The relative expressions of T-bet/GATA-3 and IFN-g/IL-4 correlated with lupus disease activity (r = 0.229, p = 0.042; r = 0.231, p = 0.040, respectively) [3].

Psychiatry related information on GATA3


High impact information on GATA3

  • Before activation, the T(H)2 cytokine locus is already associated with GATA3 and STAT6, showing some looping, but these are insufficient to induce cytokine gene expression [8].
  • Further, FOXA1 was identified as a downstream target of GATA-3 in the mammary gland [9].
  • This suggests that GATA-3 actively maintains luminal epithelial differentiation in the adult mammary gland, which raises important implications for the pathogenesis of breast cancer [9].
  • GATA-3 was found in the luminal cells of mammary ducts and the body cells of terminal end buds (TEBs) [9].
  • We identified GATA-3 as the most highly enriched transcription factor in the mammary epithelium of pubertal mice [9].

Chemical compound and disease context of GATA3


Biological context of GATA3

  • These results show that GATA3 is essential in the embryonic development of the parathyroids, auditory system and kidneys, and indicate that other GATA family members may be involved in the aetiology of human malformations [14].
  • Promoter analysis revealed that a GATA site in a cryptic promoter in the second intron was essential and sufficient for the TAL1- and LMO-dependent transcriptional activation, and GATA3 binds to this site [15].
  • Thus, our results, which expand the spectrum of HDR-associated GATA3 mutations and report the first acceptor splice site mutation, help to elucidate the molecular mechanisms that alter the function of this zinc finger transcription factor and its role in causing this developmental anomaly [16].
  • SNPs of the GATA3 gene showed an initial association to asthma-related phenotypes [17].
  • Analysis of GATA3 in the family revealed a heterozygous missense mutation resulting in a nonconservative change of a single amino acid (R276P) in the ZnF1 domain [18].

Anatomical context of GATA3


Associations of GATA3 with chemical compounds

  • The functional effects of these mutations, together with a previously reported GATA3 ZnF1 mutation and seven other engineered ZnF1 mutations, were assessed by electrophoretic mobility shift, dissociation, yeast two-hybrid and glutathione S-transferase pull-down assays [16].
  • The good prognosis group IE showed high expression of estrogen- and GATA3-regulated genes [22].
  • Meanwhile, both positive percentage and relative intensity of gene expression were lower for a type 1 cytokine-related transcription factor T-bet (31.4% and 0.142, respectively) than those for type 2 cytokine-related GATA3 (85.7% and 0.378, respectively) [23].
  • These simvastatin-conditioned DCs up-regulated GATA-3 expression and down-regulated T-bet expression in cocultured CD4+ T cells in the absence of additional simvastatin added to the coculture [24].
  • Furthermore, 416B cells treated with the DNA demethylating agent 5-azacytidine underwent megakaryocytic differentiation accompanied by a marked increase in the level of GATA-1 mRNA but not that of GATA-2 or GATA-3 [25].

Physical interactions of GATA3


Regulatory relationships of GATA3

  • In JEG-3 cells, human GATA-2 (hGATA-2) and hGATA-3 are highly expressed and both proteins bind to the alpha-subunit gene GATA element [30].
  • These data suggest that the local recruitment of GR causes repression by inhibiting transcriptional activation by GATA3, a key tissue-specific determinant of expression of Th2 cytokines [31].
  • In addition, STAT6 induces expression of the transcription factor GATA3, which also contributes to mu-opioid receptor gene transcription [32].
  • In this case, TAL1 and LMO act as cofactors for GATA3 to activate the transcription of RALDH2 [15].
  • GATA-3 suppresses IFN-gamma promoter activity independently of binding to cis-regulatory elements [33].
  • Reciprocally, ER alpha directly stimulates the transcription of the GATA-3 gene, indicating that these two factors are involved in a positive cross-regulatory loop [34].

Other interactions of GATA3

  • This member, called hGATA3, has 85% amino acid homology with hGATA1 in the DNA-binding domain and no homology elsewhere in the protein [35].
  • In contrast, GATA-2 is strongly expressed in both most primitive and committed progenitors cells, whereas GATA-3 is mostly detected in most primitive ones [36].
  • Repression of interleukin-5 transcription by the glucocorticoid receptor targets GATA3 signaling and involves histone deacetylase recruitment [31].
  • These results show, for the first time, that Ets1 and Ets2 are able to cooperate with GATA3 [2].
  • To further establish the importance of this region, we obtained 19 kb of sequence and screened for potential binding sites for the MAR-binding protein, SATB1, and for GATA-3, both of which are critical for T cell development [37].

Analytical, diagnostic and therapeutic context of GATA3


  1. Identification of GATA3 as a breast cancer prognostic marker by global gene expression meta-analysis. Mehra, R., Varambally, S., Ding, L., Shen, R., Sabel, M.S., Ghosh, D., Chinnaiyan, A.M., Kleer, C.G. Cancer Res. (2005) [Pubmed]
  2. Regulation of the human interleukin-5 promoter by Ets transcription factors. Ets1 and Ets2, but not Elf-1, cooperate with GATA3 and HTLV-I Tax1. Blumenthal, S.G., Aichele, G., Wirth, T., Czernilofsky, A.P., Nordheim, A., Dittmer, J. J. Biol. Chem. (1999) [Pubmed]
  3. Elevated Gene Expression of ThTh2 Associated Transcription Factors Is Correlated with Disease Activity in Patients with Systemic Lupus Erythematosus. Lit, L.C., Wong, C.K., Li, E.K., Tam, L.S., Lam, C.W., Lo, Y.M. J. Rheumatol. (2007) [Pubmed]
  4. Hepatic erythropoietin gene regulation by GATA-4. Dame, C., Sola, M.C., Lim, K.C., Leach, K.M., Fandrey, J., Ma, Y., Knöpfle, G., Engel, J.D., Bungert, J. J. Biol. Chem. (2004) [Pubmed]
  5. Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiation: a model for cellular decision-making. Yates, A., Callard, R., Stark, J. J. Theor. Biol. (2004) [Pubmed]
  6. Cataracts after total body irradiation and bone marrow transplantation in patients with acute leukemia in complete remission: a study of the European Group for Blood and Marrow Transplantation. Belkacemi, Y., Labopin, M., Vernant, J.P., Prentice, H.G., Tichelli, A., Schattenberg, A., Boogaerts, M.A., Ernst, P., Della Volpe, A., Goldstone, A.H., Jouet, J.P., Verdonck, L.F., Locasciulli, A., Rio, B., Ozsahin, M., Gorin, N.C. Int. J. Radiat. Oncol. Biol. Phys. (1998) [Pubmed]
  7. Early reduction in the aneuploidy at chromosomes 7 and 8 are significantly correlated with clinical effect in high-dose rate brachytherapy with external beam radiotherapy in localized prostate cancer. Kasahara, K., Taguchi, T., Inoue, K., Shuin, T., Kariya, S., Yoshida, S., Furihata, M. Int. J. Mol. Med. (2001) [Pubmed]
  8. SATB1 packages densely looped, transcriptionally active chromatin for coordinated expression of cytokine genes. Cai, S., Lee, C.C., Kohwi-Shigematsu, T. Nat. Genet. (2006) [Pubmed]
  9. GATA-3 Maintains the Differentiation of the Luminal Cell Fate in the Mammary Gland. Kouros-Mehr, H., Slorach, E.M., Sternlicht, M.D., Werb, Z. Cell (2006) [Pubmed]
  10. Mutation of GATA3 in human breast tumors. Usary, J., Llaca, V., Karaca, G., Presswala, S., Karaca, M., He, X., Langerød, A., Kåresen, R., Oh, D.S., Dressler, L.G., Lønning, P.E., Strausberg, R.L., Chanock, S., Børresen-Dale, A.L., Perou, C.M. Oncogene (2004) [Pubmed]
  11. 3D interstitial HDR brachytherapy combined with 3D external beam radiotherapy and androgen deprivation for prostate cancer. Preliminary results. Martin, T., Hey-Koch, S., Strassmann, G., Kolotas, C., Baltas, D., Rogge, B., Röddiger, S., Vogt, H.G., Heyd, R., Dannenberg, T., Kurek, R., Tunn, U., Zamboglou, N. Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]. (2000) [Pubmed]
  12. Outpatient interstitial thermoradiotherapy. Lee, D.J., Mayer, R., Hallinan, L. Cancer (1996) [Pubmed]
  13. Results of histo-pathologic examination of three enucleated eyes with a choroidal melanoma after strontium-90 irradiation. Parys-van Ginderdeuren, R., van den Oord, J.J., Missotten, L. Bulletin de la Société belge d'ophtalmologie. (1997) [Pubmed]
  14. GATA3 haplo-insufficiency causes human HDR syndrome. Van Esch, H., Groenen, P., Nesbit, M.A., Schuffenhauer, S., Lichtner, P., Vanderlinden, G., Harding, B., Beetz, R., Bilous, R.W., Holdaway, I., Shaw, N.J., Fryns, J.P., Van de Ven, W., Thakker, R.V., Devriendt, K. Nature (2000) [Pubmed]
  15. TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3. Ono, Y., Fukuhara, N., Yoshie, O. Mol. Cell. Biol. (1998) [Pubmed]
  16. Characterization of GATA3 mutations in the hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome. Nesbit, M.A., Bowl, M.R., Harding, B., Ali, A., Ayala, A., Crowe, C., Dobbie, A., Hampson, G., Holdaway, I., Levine, M.A., McWilliams, R., Rigden, S., Sampson, J., Williams, A.J., Thakker, R.V. J. Biol. Chem. (2004) [Pubmed]
  17. Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes. Pykäläinen, M., Kinos, R., Valkonen, S., Rydman, P., Kilpeläinen, M., Laitinen, L.A., Karjalainen, J., Nieminen, M., Hurme, M., Kere, J., Laitinen, T., Lahesmaa, R. J. Allergy Clin. Immunol. (2005) [Pubmed]
  18. Functional analysis of a novel GATA3 mutation in a family with the hypoparathyroidism, deafness, and renal dysplasia syndrome. Zahirieh, A., Nesbit, M.A., Ali, A., Wang, K., He, N., Stangou, M., Bamichas, G., Sombolos, K., Thakker, R.V., Pei, Y. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  19. c-Maf and JunB mediation of Th2 differentiation induced by the type 2 G protein-coupled receptor (VPAC2) for vasoactive intestinal peptide. Voice, J., Donnelly, S., Dorsam, G., Dolganov, G., Paul, S., Goetzl, E.J. J. Immunol. (2004) [Pubmed]
  20. Chromatin remodeling at the Th2 cytokine gene loci in human type 2 helper T cells. Kaneko, T., Hosokawa, H., Yamashita, M., Wang, C.R., Hasegawa, A., Kimura, M.Y., Kitajiama, M., Kimura, F., Miyazaki, M., Nakayama, T. Mol. Immunol. (2007) [Pubmed]
  21. Human GATA-3: a lineage-restricted transcription factor that regulates the expression of the T cell receptor alpha gene. Ho, I.C., Vorhees, P., Marin, N., Oakley, B.K., Tsai, S.F., Orkin, S.H., Leiden, J.M. EMBO J. (1991) [Pubmed]
  22. Estrogen-regulated genes predict survival in hormone receptor-positive breast cancers. Oh, D.S., Troester, M.A., Usary, J., Hu, Z., He, X., Fan, C., Wu, J., Carey, L.A., Perou, C.M. J. Clin. Oncol. (2006) [Pubmed]
  23. Type two cytokines predominance of human lung cancer and its reverse by traditional Chinese medicine TTMP. Wei, H., Sun, R., Xiao, W., Feng, J., Zhen, C., Xu, X., Tian, Z. Cell. Mol. Immunol. (2004) [Pubmed]
  24. Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells. Arora, M., Chen, L., Paglia, M., Gallagher, I., Allen, J.E., Vyas, Y.M., Ray, A., Ray, P. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  25. Megakaryocytic differentiation induced in 416B myeloid cells by GATA-2 and GATA-3 transgenes or 5-azacytidine is tightly coupled to GATA-1 expression. Visvader, J., Adams, J.M. Blood (1993) [Pubmed]
  26. GATA-3 is an important transcription factor for regulating human NKG2A gene expression. Marusina, A.I., Kim, D.K., Lieto, L.D., Borrego, F., Coligan, J.E. J. Immunol. (2005) [Pubmed]
  27. Distal regulatory elements play an important role in regulation of the human IL-5 gene. Urwin, D.L., Schwenger, G.T., Groth, D.M., Sanderson, C.J. Eur. J. Immunol. (2004) [Pubmed]
  28. Lipid defect underlies selective skin barrier impairment of an epidermal-specific deletion of Gata-3. de Guzman Strong, C., Wertz, P.W., Wang, C., Yang, F., Meltzer, P.S., Andl, T., Millar, S.E., Ho, I.C., Pai, S.Y., Segre, J.A. J. Cell Biol. (2006) [Pubmed]
  29. Interaction of GATA-3/T-bet transcription factors regulates expression of sialyl Lewis X homing receptors on Th1/Th2 lymphocytes. Chen, G.Y., Osada, H., Santamaria-Babi, L.F., Kannagi, R. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  30. GATA-binding proteins regulate the human gonadotropin alpha-subunit gene in the placenta and pituitary gland. Steger, D.J., Hecht, J.H., Mellon, P.L. Mol. Cell. Biol. (1994) [Pubmed]
  31. Repression of interleukin-5 transcription by the glucocorticoid receptor targets GATA3 signaling and involves histone deacetylase recruitment. Jee, Y.K., Gilmour, J., Kelly, A., Bowen, H., Richards, D., Soh, C., Smith, P., Hawrylowicz, C., Cousins, D., Lee, T., Lavender, P. J. Biol. Chem. (2005) [Pubmed]
  32. Cannabinoid receptor type 2 agonists induce transcription of the mu-opioid receptor gene in Jurkat T cells. Börner, C., Höllt, V., Kraus, J. Mol. Pharmacol. (2006) [Pubmed]
  33. GATA-3 suppresses IFN-gamma promoter activity independently of binding to cis-regulatory elements. Kaminuma, O., Kitamura, F., Kitamura, N., Miyagishi, M., Taira, K., Yamamoto, K., Miura, O., Miyatake, S. FEBS Lett. (2004) [Pubmed]
  34. Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer. Eeckhoute, J., Keeton, E.K., Lupien, M., Krum, S.A., Carroll, J.S., Brown, M. Cancer Res. (2007) [Pubmed]
  35. A T-cell specific TCR delta DNA binding protein is a member of the human GATA family. Joulin, V., Bories, D., Eléouet, J.F., Labastie, M.C., Chrétien, S., Mattéi, M.G., Roméo, P.H. EMBO J. (1991) [Pubmed]
  36. Expression of tal-1 and GATA-binding proteins during human hematopoiesis. Mouthon, M.A., Bernard, O., Mitjavila, M.T., Romeo, P.H., Vainchenker, W., Mathieu-Mahul, D. Blood (1993) [Pubmed]
  37. Identification of a candidate regulatory region in the human CD8 gene complex by colocalization of DNase I hypersensitive sites and matrix attachment regions which bind SATB1 and GATA-3. Kieffer, L.J., Greally, J.M., Landres, I., Nag, S., Nakajima, Y., Kohwi-Shigematsu, T., Kavathas, P.B. J. Immunol. (2002) [Pubmed]
  38. Identification of a novel insertion mutation in GATA3 with HDR syndrome. Mino, Y., Kuwahara, T., Mannami, T., Shioji, K., Ono, K., Iwai, N. Clin. Exp. Nephrol. (2005) [Pubmed]
  39. Direct and indirect effects of retinoic acid on human Th2 cytokine and chemokine expression by human T lymphocytes. Dawson, H.D., Collins, G., Pyle, R., Key, M., Weeraratna, A., Deep-Dixit, V., Nadal, C.N., Taub, D.D. BMC Immunol. (2006) [Pubmed]
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